Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/β-lactamase inhibitor combination approved for the treatment of multidrug-resistant Gram-negative bacteria. It shows activity against β-lactamases of Classes A, C, and D (Oxa-48), but not against metallo-β-lactamases (MBLs). In this study, the in vitro activity of CAZ-AVI was evaluated against clinical isolates of Klebsiella pneumoniae, both KPC producers and non-producers, collected as part of the global ATLAS surveillance program. A total of 1137 non-duplicate isolates of K. pneumoniae, collected from different infection sites in hospitals in Brazil between 2018 and 2023, were evaluated. Susceptibility testing was determined using broth microdilution and susceptibility profiles were analyzed according to BrCAST (2025) breakpoints. Carbapenemase-encoding genes were investigated by PCR followed by sequencing. Overall, CAZ-AVI was the antibiotic with the best in vitro activity (93.4% susceptibility; MIC50/90, 0.5/4.0 mg/L) compared to meropenem (58.3% susceptibility; MIC50/90, 0.125/>16 mg/L) and colistin (84.4% susceptibility; MIC50/90, 0.25/>8 mg/L). CAZ-AVI maintained potent in vitro activity each year, with MIC50 values of 0.25 mg/L (2018) and 0.5 mg/L (2019, 2020, 2022, 2023) and MIC90 values of 2.0 mg/L (2018, 2019) and 4.0 mg/L (2020–2023). In 2018 and 2023, 100% and 90.3% of isolates, respectively, were susceptible to CAZ-AVI. Susceptibility to colistin (∼85%) and gentamicin (∼62%) remained stable over the years, but a significant decrease was observed for meropenem (77% in 2018 – 57.4% in 2023) and cefepime (50% in 2018 – 35.8% in 2023). Of the isolates, 402 (35.3%) were positive for KPC (KPC-2, 94.7%). Among these, susceptibility to CAZ-AVI was 94.5% (MIC50/90, 1.0/4.0 mg/L). Of the 75 (6.6%) isolates resistant to CAZ-AVI, 51 were positive only for NDM-1, 21 showed coproduction of carbapenemases (20 for KPC-2+NDM-1 and one for KPC-2+IMP-1), one isolate was positive only for KPC, one isolate positive only for IMP-1, and one isolate in which carbapenemases were not detected. The results demonstrated that CAZ-AVI showed potent in vitro activity against the K. pneumoniae isolates evaluated, including those positive for KPC. Resistance to CAZ-AVI observed in this study was associated with the production of MBLs, especially NDM-1, as well as the coproduction of KPC+NDM.
Fehlberg et al. (Sun,) studied this question.
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